The aim of this proposal is to help resolve the controversy surrounding carbohydrate-Ia antigens (CHO-Ia) and provide additional information on the immunobiology and structure of these antigens using a combined chemical, serological and functional approach. (1) The chemical composition and structure of CHO-Ia antigens will be defined using techniques of carbohydrate and lipid chemistry. (2) Monoclonal antibodies to CHO-Ia antigens will continue to be characterized and used to aid in the purification and analysis of CHO-Ia antigens as well as in functional studies to determine CHO-Ia involvement in I-region responses. (3) The mechanism behind the regulation of antibody production to CHO-Ia antigens and the subsequent tolerance to allo-CHO-Ia immunization will be pursued. The possibility that antibody production to allo-CHO-Ia antigens is under anti-idiotypic regulation will be tested by determining the nature of the regulatory material using immunoabsorbants and/or physiochemical methods of analysis. The possibility that T cell allo-reactivity has been compromised in CHO-Ia tolerant mice will be tested by assessing I-region determined MLR and GVHR competency in suppressed animals. Suppression of antibody production and tolerance to allo-CHO-Ia antigens will be further investigated using serum and cell transfer experiments. (4) Finally, the hypothesis that protein-Ia possesses glycosyltransferase activity and is responsible for synthesis of CHO-Ia antigens will be explored. The enzymatic function of protein-Ia and the substrate role of CHO-Ia will be tested using both chemical and serological approaches. The data from these four interrelated areas will help to determine the role that CHO-Ia antigens play in I-region associated responses and provide information on the relationship between protein-Ia and CHO-Ia antigens.